Treatment of recurrent genotype 4 hepatitis C after liver transplantation: early virological response is predictive of sustained virological response. An AISF RECOLT-C group study

Introduction. Hepatitis C virus genotype 4 is predominant in the Middle East and Northern Africa, even if it has recently spread to Southern Europe. Data about the treatment of post-liver transplantation (LT) genotype 4 hepatitis C recurrence are scarce. We report a retrospective analysis of post-LT genotype 4 hepatitis C treatment in 9 Italian transplant centres, focusing on the overall survival rates and treatment outcome.Results. Among 452 recipients, we identified 17 HCV genotype 4 patients (16 males, 1 female) transplanted between 1998 and 2007. All patients received combined antiviral treatment with conventional doses of interferon (recombinant or pegylated) and ribavirin after histological diagnosis of hepatitis C recurrence. The observed overall survival after LT was 100% at 1 year and 83.3% at 5 years. More than 1/3 (35.3%) of patients achieved a sustained virological response (SVR) and 40% (data available in 15 subjects) an early virological response (EVR), which was significantly associated with the achievement of SVR (overall accuracy: 85.7%; predictive values of EVR absence/presence 80/88.8%; chi-square p < 0.05).Conclusion. In conclusion, in post-LT genotype 4 hepatitis C treatment, SVR rates are similar to genotype 1. Patients who don’t show an EVR are not likely to achieve a SVR.     

干扰素治疗慢性丙型肝炎获得快速和早期病毒学应答的影响因素

目的:探讨慢性丙型肝炎患者应用聚乙二醇干扰素(pegylated interferon,PEG-IFN)联合利巴韦林治疗不同病毒学应答模式与疗效的关系及获得快速和早期病毒学应答的预测因素,为临床抗病毒治疗疗效判定和治疗方案的选择提供依据.方法:81例慢性丙型肝炎患者均给予pegylated interferon alpha-2a(PEG-IFNα-2a)135-180μg或PEG-IFNα-2b50-80μg,1次/wk皮下注射;利巴韦林800-1200mg/d,对所有患者进行治疗前、治疗4、12、24、48wk和停药后至少24wk的随访,详细记录患者的性别、年龄、丙型肝炎病毒(hepatitis C virus,HCV)RNA水平、肝硬化程度、脂肪肝、体质量指数(body mass index,BMI)、糖尿病史、饮酒史、输血史、既往抗病毒治疗史等等.根据治疗情况将患者分为快速病毒学应答(rapid virological response,RVR)组、早期病毒学应答(early virological response,EVR)组、无应答(no response,NR)组、复发(relapse,RL)组和持续病毒学应答(sustained virologic response,SVR)组.分别应用单因素分析和多因素Logistic逐步回归分析方法分析获得RVR和EVR的影响和预测因素.结果:81例患者中51例(62.9%)获得RVR,65例(80.2%)获得EVR,65例(80.2%)获得SVR,10例(12.3%)NR,6例(7.4%)FL.RVR组88.2%获得SVR,EVR组90.8%获得SVR.未获RVR和EVR的患者16人(19.8%),其中6人(37.5%)获得SVR,6人(100%)均未复发.3组SVR率的差异有统计学意义(?2=20.622,P<0.05),复发率差异无统计学意义(P>0.05).SVR、NR和RL组的RVR率分别为69.2%、0%、100.0%;EVR率分别为90.8%、0%、100.0%.3组RVR率及EVR率的差异有统计学意义.单因素分析结果显示:年龄≤40岁,HCVRNA载量<4×105,无肝硬化与快速病毒学应答有关;年龄≤40岁,HCVRNA载量<4×105,无肝硬化,BMI<24kg/m2与早期病毒学应答有关.将上述指标进行多因素Logistic逐步回归分析,结果表明:基线HCVRNA载量和肝硬化是预测RVR和EVR的独立影响因素.结论:RVR和EVR的获得是获得SVR的重要预测因素;未获得RVR和EVR的患者通过1年疗程的治疗,少部分患者仍可获得SVR;RVR和EVR不能预测复发.年龄、基线病毒载量、有无肝硬化和体质量指数与RVR和EVR的获得密切相关.基线病毒载量、有无肝硬化是预测RVR和EVR的独立因素.     

Combined treatment with pegylated interferon (alpha-2b) and ribavirin in the acute phase of hepatitis C virus recurrence after liver transplantation

BACKGROUND/AIMS: The efficacy and safety of treatment with pegylated interferon alpha-2b (Peg-Intron, 1.5 microg/kg) and ribavirin (400-800 mg) in the acute phase of recurrent HCV after LT is presented. METHODS: Twenty-four patients (17 men) transplanted for HCV-associated cirrhosis (genotype 1b) were treated for at least 6 months and compared with 24 consecutive transplant patients (16 men) without antiviral therapy (controls). RESULTS: At completion of treatment, 14/24 treated patients (58%) achieved HCV-RNA negativity, compared to none of controls (P<0.0001). Sustained virological response (SVR) occurred in 8/23 treated patients (34.7%) who reached week 24 after treatment and none of controls (P<0.005). At 12 weeks after treatment, 15/24 patients (62.5%) had an early virological response (EVR) (seven tested HCV-RNA negative). SVR was associated with absence of corticosteroid bolus administration (P=0.01), presence of EVR (P=0.002) and absence of cytomegalovirus infection (P=0.001). Haematological adverse effects included anaemia, 17/24 cases (71%) and leukopenia, 23/24 cases (96%). One patient presented mild acute rejection that resolved by adjusting immunosuppressive dose. CONCLUSIONS: Treatment with pegylated interferon alpha-2b plus ribavirin in the acute phase of HCV reinfection yielded an EVR of 62.5% and a SVR of 34.7%. The combination was safe, with a low rate of therapy withdrawal.     

Predictive value of rapid virological response and early virological response on sustained virological response in HCV patients treated with pegylated interferon alpha-2a and ribavirin

BACKGROUND AND AIM: The therapeutic effect of pegylated interferon (peg-IFN)-alpha-2a combination with ribavirin on patients with chronic hepatitis C virus (HCV) infection is dependent on the rapidity of the virological response. The aim of this study was to investigate the predictive value of rapid virological response (RVR) and early virological response (EVR) on sustained virological response (SVR) in HCV patients treated with peg-IFN-alpha-2a and ribavirin. METHODS: The HCV genotypes of 105 patients with chronic hepatitis C were detected by enzyme-immunoassay. Patients received subcutaneous 180 microg peg-IFN-alpha-2a once weekly plus daily ribavirin. Patients with genotype 1 were treated for 48 weeks and patients with genotype 2 or 3 were treated for 24 weeks. HCV RNA was assessed by qualitative PCR at pretreatment, at weeks 4 and 12 during treatment, and at week 24 of follow-up. Virological response rates at different weeks were investigated, with RVR defined as serum HCV RNA undetectable after 4 weeks and EVR defined as HCV RNA either undetectable or decrease by >or=2 log(10) after 12 weeks. The effects of virological response rates at different weeks on SVR were analyzed. RESULTS: Of the 105 patients, 44 (41.9%) were genotype 1, 46 (43.8%) were genotype 2, and 15 (14.3%) were genotype 3. RVR rates (19.5%) of patients with genotype 1 were significantly lower than those (60.7%) of genotype 2 or 3 (chi(2) = 16.836, P = 0.000); and EVR rates (73.2%) of patients with genotype 1 were significantly lower than those (96.7%) of genotype 2 or 3 (chi(2) = 12.220, P = 0.000). The SVR rates (86.7%) of patients who had achieved RVR were significantly higher than those (43.9%) of patients who had not achieved RVR (chi(2) = 19.713, P = 0.000). The positive predictive value of RVR in all patients was higher than that of EVR, but there was no significant difference between RVR and EVR. The negative predictive value of RVR in all patients or with genotype 1 was significantly lower than that of EVR. In univariate analysis, HCV RNA level (P = 0.014), genotype (P = 0.001), RVR (P = 0.000) and EVR (P = 0.000) were associated with effect of treatment. However, in stepwise regression analysis, the independent factors associated with effect of antiviral therapy were RVR (OR = 6.501, P = 0.001), EVR (OR = 2.776, P = 0.003) and genotype (OR = 3.061, P = 0.024). CONCLUSIONS: The RVR and EVR rates of patients with genotype 1 were significantly lower than those of patients with genotype 2 or 3. RVR had a similar predictive value as EVR on SVR. Genotype, HCV RNA level, RVR and EVR were associated with SVR. Genotype, RVR and EVR were independent factors for predicting the effect of antiviral therapy.     

Retreatment with pegylated interferon alpha-2a and ribavirin in patients with chronic hepatitis C who have relapsed or not responded to a first course of pegylated interferon-based therapy

BACKGROUND

Pegylated interferon (pegIFN) and ribavirin combination therapy remains the first-line treatment for chronic hepatitis C virus (HCV) infection. In contrast to the wealth of studies in treatment-naive patients, the effectiveness of retreatment in patients who have previously failed pegIFN-based therapy is largely unreported.

AIM:

To assess the effectiveness of the retreatment of patients who have previously failed an initial course of pegIFN-based therapy with pegIFNα-2a and ribavirin.

METHODS:

A post-hoc analysis of a multicentre open-label study was performed. Patients received pegIFNα-2a and ribavirin at a dose of 800 mg/day and later 1000 mg/day to 1200 mg/day for 24 to 48 weeks at the discretion of the investigator. Outcomes at week 12 (early virological response [EVR]) and week 24 (sustained virological response [SVR]) were analyzed.

RESULTS:

Eighty-seven patients who had relapsed after previous pegIFN-based therapy (n=28; 78% genotype 1) or were nonresponders (n=59; 71% genotype 1) were analyzed. Of the relapsers, 86% achieved an EVR and 68% achieved an SVR. In relapsers to pegIFN monotherapy (n=15) or pegIFN plus ribavirin (n=13), 60% and 77% achieved an SVR, respectively. Fibrosis and genotype did not affect the likelihood of SVR in relapsers although this may be the result of the relatively small number of patients. In previous nonresponders, an EVR was achieved in 53% but an SVR occurred in only 17%. In nonresponders to pegIFN monotherapy (n=9) and pegIFN plus ribavirin (n=50), 33% and 14% achieved an SVR, respectively. Genotype did not affect SVR in nonresponders. Only 10% with a METAVIR score of F3 or F4 on liver biopsy achieved an SVR.

CONCLUSIONS:

Relapse after previous pegIFN-based therapy is associated with a strong probability of treatment success whereas retreatment of those with previous nonresponse does not.     

Twenty-four weeks of pegylated interferon plus ribavirin effectively treat patients with HCV genotype 6a

The optimal duration of treatment and expected response rate for hepatitis C virus genotype (HCV-6)-infected patients have not been determined. Our aims were to determine the treatment outcome with pegylated interferon (PEG-IFN) plus ribavirin for HCV-6a-infected patients at Southwest Hospital and assess the association of the on-treatment virological response with the sustained virological response (SVR). Medical records were reviewed retrospectively. Twenty-two HCV-6a-infected patients were treated for 24 weeks, and 21 (95.5%) achieved an early virological response (EVR), 20 (90.9%) an end-of-treatment response (ETR) and 18 (81.8%) a SVR. However, only 18 of the 22 HCV-6a-infected patients were tested for serum HCV RNA level at week 4 of treatment and 15 (83.3%) achieved a rapid virological response (RVR). The rates of SVR, RVR, EVR and ETR in these patients were all similar to those in HCV-2/3 treated for 24 weeks and higher than those in HCV-1b-infected patients treated for 48 weeks. A lower relapse rate (10.0%) was seen in HCV-6a compared with HCV-2/3 (12.5%) or HCV-1b-infected patients (23.3%). The positive predictive values of RVR and EVR for HCV-6a were comparable with those for HCV-2/3-infected patients (86.7%vs 90.9%, P = 0.683 and 85.7%vs 86.8%, P = 0.904, respectively). Of the 3 HCV-6a-infected patients who did not achieve a RVR, 2 achieved an EVR and went on to achieve a SVR. The patient who did not achieve an EVR did not achieve a SVR. In summary, our results indicate that 24 weeks of PEG-IFN plus ribavirin can effectively treat patients with HCV-6a chronic infection.     

Peginterferon-α-2b and Ribavirin for Hepatitis C Recurrence Postorthotopic Liver Transplantation

GOALS:: To evaluate the safety and efficacy of peginterferon-α-2b plus ribavirin in patients with recurrent hepatitis C after orthotopic liver transplant. BACKGROUND:: Reinfection of liver allografts in hepatitis C virus -infected transplant recipients begins immediately after transplantation. Treatment of these patients is challenging because of poor tolerability. STUDY:: A multicenter, open-label study enrolling patients with persistent viremia after primary orthotopic liver transplant for cirrhosis related to hepatitis C virus infection. Patients received peginterferon-α-2b (1.5 μg/kg/wk) plus ribavirin (400 to 1200 mg/d administered using a dose-escalating regimen and according to body weight) for 48 weeks. The primary endpoint was sustained virologic response (SVR). RESULTS:: In total, 125 patients started treatment and 58.4% completed 48 weeks. SVR rate was 28.8% (G1, 23.8%; G2/3, 55.0%), end-of-treatment response rate was 40.8%, and relapse rate was 18.2%. SVR was 55% among patients who completed treatment. Genotype 2/3 infection, male sex, baseline hemoglobin>14 g/dL, 80:80:80 compliance, rapid virologic response (RVR), and complete early virologic response (cEVR) were predictors of SVR. SVR was higher among patients with RVR compared with those without RVR (83.3% vs. 25.7%; P=0.0098), and among patients with cEVR compared with those without EVR (66.7% vs. 1.8%; P<0.0001). Thirty-eight patients discontinued because of an adverse event and 69 required dose reduction or interruption. Anemia (74%) and neutropenia (30%) were common, and rejection was low (3.2%). CONCLUSIONS:: SVR was low in this study. Anemia was a particular challenge in achieving maximal ribavirin therapeutic exposure and may account in part for the lower SVR.     

Effectiveness and tolerability of pegylated Interferon alpha-2a and ribavirin combination therapy in Romanian patients with chronic hepatitis C: from clinical trials to clinical practice

BACKGROUND AND AIM: Pegylated interferon alpha in combination with ribavirin represents nowadays the gold standard therapy in patients with chronic hepatitis C. The aim of this study was to assess early (EVR) and sustained virological response (SVR), tolerability and baseline predictive factors for SVR in patients with chronic hepatitis C treated with peginterferon alpha-2a and ribavirin combination therapy in day-to-day clinical practice. METHODS: The analysis included 174 consecutive patients with chronic hepatitis C (naive, relapsers and non-responders after standard therapy) managed in two expertise gastroenterology centers in Romania, mainly on an outpatient basis. The combination therapy was initiated between 1st of June 2002 - 30th of June 2003. RESULTS: The mean age of the study population was 47 years; 41% were men, mean BMI was 26.5 kg/sq.m. Only 7.5% of them had bridging fibrosis/cirrhosis on liver biopsy. EVR and SVR were noted in 78.7% and 51.1%, respectively. Multivariate analysis showed two independent variables associated with SVR: absence of bridging fibrosis/cirrhosis and absence of hepatic steatosis. The rate and profile of side effects associated with pegylated interferon alpha-2a and ribavirin in our clinical setting were all predictable, based on previous experience in the literature. Side effects resulted in interferon and ribavirin dose reductions in 9.2% and, respectively, 25.3%, but permanent discontinuation of the combination therapy was required in only 5.74% of patients. CONCLUSION: Combination antiviral therapy can be safely and successfully used outside clinical trials. To achieve high response rates and tolerability, similar or better than those reported in clinical trials, hepatitis C patients have to be managed in expertise centers, by experienced physicians, aiming at minimizing side effects, optimizing dosing, and enhancing compliance.     

Different doses of consensus interferon plus ribavirin in patients with hepatitis C virus genotype 1 relapsed after interferon monotherapy： A randomized controlled trial

INTRODUCTION Retreatment of hepatitis C patients who relapsed after recombinant interferon (rIFN) monotherapy has a fair rate of success when ribavirin is added to the original protocol. About 30% of patients infected with hepatitis C virus (HCV) genotype…     

Triple therapy of initial high-dose interferon with ribavirin and amantadine for patients with chronic hepatitis C

Aims: We previously reported the potential effect of combination therapy of an initial high‐dose interferon (IFN) and amantadine on the eradication of HCV‐RNA in patients with chronic hepatitis C. The additive effects of amantadine on interferon and ribavirin combination therapy remain controversial. In this study we investigated the efficacy of initial high‐dose IFN with ribavirin and amantadine on the virological response in patients with chronic hepatitis C with a high viral load of genotype 1b. Methods: Twenty‐two patients with high viral loads of genotype 1b hepatitis C virus were enrolled in this pilot study. Patients were administered IFN‐beta for four weeks and then IFN‐alpha2b for 22 weeks with daily oral administration of ribavirin and amantadine. Results: A sustained virological response (SVR) was shown in 31.8% (seven of 22 patients). With the naïve patients, the SVR rate was 21.4% (three of 14 patients). In patients who could not eradicate HCV‐RNA by previous IFN monotherapy, the SVR rate was 50% (four of eight patients). Conclusion: Triple therapy with an initial high dose of IFN with ribavirin and amantadine may be effective, especially for chronic hepatitis C IFN‐retreatment patients with a high viral load of genotype 1b.     

Peginterferon alpha-2a and ribavirin versus peginterferon alpha-2a monotherapy in early virological responders and peginterferon alpha-2a and ribavirin versus peginterferon alpha-2a, ribavirin and amantadine triple therapy in early virological nonresponders: the SMIEC II trial in naïve patients with chronic hepatitis C

OBJECTIVE: The objective of this study was to compare the efficacy of anti-hepatitis C virus (anti-HCV) treatment schedules on the basis of an early virological response (EVR), defined as undetectable serum HCV-RNA (<50 IU/ml) after a 12-week induction course of peginterferon alpha-2a (PEG-IFN) 180 mcg/week. METHODS: A total of 210 interferon-na?ve patients (69% male; median age, 42 years) with histologically proven chronic hepatitis C infection (genotype 1: 62%) received PEG-IFN 180 mcg/week for 12 weeks. Patients with EVR (58%) were randomized to continue PEG-IFN monotherapy (n=64) or to add ribavirin (RBV), 800 mg/day (n=57), for 36 additional weeks. Patients without EVR (42%) were randomized to add RBV (n=42), or RBV plus amantadine, 200 mg/day (n=47), for 36 additional weeks. Sustained virological response (SVR, undetectable HCV-RNA 24 weeks after treatment completion) was compared among treatment groups. RESULTS: Patients with EVR: SVR rate was 60.3% in the PEG-IFN group versus 67.2% in the PEG-IFN+RBV group (NS). In genotypes 2/3, SVR rates were 66.7 versus 73.1% (NS); in genotypes 1/4, SVR rates were 51.6 versus 61.3%, respectively (NS). Patients without EVR: SVR was 16.7% in the PEG-IFN+RBV group versus 31.9% in the triple therapy group (P=0.07). In patients with genotypes 1/4, SVR rates were 9.4 versus 29.7% (P=0.041). CONCLUSION: In genotypes 1/4 patients without EVR, triple therapy results in higher SVR rates than standard dual therapy. This study confirms that addition of amantadine is beneficial in early-recognized 'difficult-to-treat' patients.     

Systematic review of the treatment of established recurrent hepatitis C with pegylated interferon in combination with ribavirin

The aim of our study was to conduct a systematic review of studies evaluating antiviral therapy with pegylated interferon (PEG-IFN) alfa in combination with ribavirin for the management of recurrent hepatitis C after liver transplantation. Data sources included electronic databases and a manual search. Studies evaluating the efficacy and tolerability of PEG-IFN alfa with ribavirin in patients with recurrent hepatitis C were selected for inclusion. The information extracted from each of the selected publications included study design details, patient characteristics, treatment regimens and efficacy and tolerability end points. Nineteen studies including 611 patients were identified. PEG-IFN alfa-2b was used in 16 studies. The mean rate of SVR was 30.2% (range, 8-50%). Dose reduction and discontinuation of treatment were common in these studies (73% and 27.6%, respectively). The lack of an early virologic response (EVR) at 3months of therapy was the most frequently described predictive factor of nonresponse. Treatment discontinuation and dose reductions due to adverse events were frequent and possibly represent important obstacles to attainment of SVR. EVR at 3months of treatment should be considered an important predictor of treatment outcome.     

Efficacy and tolerability of low-dose interferon-α in hemodialysis patients with chronic hepatitis C virus infection

AIM:To evaluate the efficacy and tolerability of lowdose standard or pegylated interferon(PEG-IFN)in hepatitis C virus(HCV)-positive hemodialysis patients.METHODS:In total,19 patients were enrolled in this study,of which 12 received PEG-IFNα-2a 67.5μg 1time/wk(Group 1)and 7 received standard interferonα-2b subcutaneously 1.5×106 U 3 times/wk(Group2).The treatment durations were 48 wk for patients infected with HCV genotype 1 and 24 wk for patients infected with HCV genotype 2/3.All patients were prospectively followed after the completion of therapy.The efficacy and tolerability of the treatment were evaluated based on the sustained virological response(SVR)and treatment-related drop-out rate.RESULTS:In Group 1,11 of the 12 patients completed the treatment.Early virological response(EVR)and sustained virological response(SVR)rates were 83.3%and 91.7%,respectively.One patient withdrew from treatment due to an adverse event(leukopenia).The drop-out rate was 8.3%in this group.In Group 2,5 of the 7 patients completed the treatment with an EVR and SVR of 85.7%and 71.4%,respectively.Two patients withdrew due to treatment-related adverse events(nausea and depression).In this group,the drop-out rate was 28.6%.In total,16 of the patients attained EVR,and 15 of them completed the treatment.The SVR rate for the patients who attained EVR was93.7%.Anemia was the most frequent side effect and was observed in 10/19 patients(55.5%),but could be effectively managed with erythropoietin.CONCLUSION:Low-dose interferon monotherapy,either with PEG-IFNα-2a or standard interferonα-2b,is an effective treatment option for hemodialysis patients with chronic hepatitis C.     

Role of hepatitis C virus substitutions and interleukin‐28B polymorphism on response to peginterferon plus ribavirin in a prospective study of response‐guided therapy

Recent studies have indicated that amino acid (aa) substitutions in the core region and NS5A interferon sensitivity‐determining region (ISDR) of hepatitis C virus (HCV) as well as genetic polymorphisms in the interleukin‐28B (IL‐28B) locus affect the outcome of interferon (IFN)‐based therapies. We aimed to investigate the role of these factors on response to peginterferon plus ribavirin in a prospective study of response‐guided therapy. The aa sequences in core region and ISDR and rs12979860 genotypes were analysed in 115 HCV‐1 patients. The treatment was 24 weeks for patients achieving a rapid virological response (RVR), 48 weeks for those with an early virological response (EVR) and early terminated in those without an EVR. A sustained virological response (SVR) was achieved in 82% of 34 RVR patients, 45% of 74 EVR patients and 0% of seven non‐EVR patients. Logistic regression analysis showed that ISDR mutation (≥2) [odds ratio(OR): 6.024], double core 70/91 mutations (OR: 0.136), and platelet counts ≥ 15 × 10⁴/μL (OR: 3.119) were independent pretreatment factors associated with SVR. Apart from rs12979860 CC genotype, low viral load and ISDR mutation (≥2) were significant factors predictive of RVR. Combination of rs12979860 genotype and baseline viral characteristics (viral load and core/ISDR mutations) could predict RVR and SVR with positive predictive value of 100% and 91%, and negative predictive value of 80% and 54%, respectively. In conclusion, pretreatment screening rs12979860 genotype and aa substitutions in the core region and ISDR could help identifying patients who are good candidates for peginterferon plus ribavirin therapy.     

Randomized trial of three different regimens for 24 weeks for re-treatment of chronic hepatitis C patients who failed to respond to interferon-alpha monotherapy in Taiwan.

With the favorable result of interferon (IFN)-ribavirin combination therapy for 24 weeks among naive Taiwanese chronic hepatitis C (CHC) patients, the optimal regimens of re-treatment for CHC patients who failed initial IFN monotherapy is not well-established. The study evaluated the effectiveness of re-treatment for 24 weeks with 3 different regimens and predictors for sustained virological response (SVR). METHODS: Total 120 Taiwanese CHC patients (81 males, 70 relapsers, mean age: 48.6 years) who failed initial IFN monotherapy were enrolled. They were assigned randomly (with a ratio of 1:1:2) to receive one of the three regimens for re-treatment for 24 weeks; group A: IFN 6 million units (MU) monotherapy (N=30), group B: combination therapy with ribavirin and IFN 3 MU (N=30) or group C: combination therapy with ribavirin and IFN 6 MU (N=60). The intention-to-treat rate of sustained virological response (SVR) was 38.3%. The SVR rate in group C (53.3%) was significantly higher than group A (16.7%, P<0.005) and group B (30%, P<0.05). Drop-out rates were similar between the three groups. Patients achieving SVR had significant improvement histologically. Hepatitis C virus (HCV) genotype non-1b infection, lower pretreatment HCV RNA levels, combined with ribavirin and with higher IFN dose, and relapsers were independent predictors for SVR. CONCLUSION: We concluded that more than one-third Taiwanese CHC patients achieved SVR after 24 weeks re-treatment and combination therapy, especially with higher dose of IFN, yielded higher efficacy.     

Differential viral kinetics in treated genotype 4 chronic hepatitis C patients according to ethnicity

Summary.  Data concerning the efficacy of PEG-IFNα2a plus ribavirin treatment in treatment-naïve, genotype 4-infected chronic hepatitis C (CHC) patients from Europe are limited. Hence the aim of this study was to investigate the viral kinetics as well as the sustained virological response (SVR) rates and their predictors, in these patients. One hundred and twenty-three patients were retrospectively analysed. Early (EVR) and late virological response (LVR) was confirmed by undetectable (<50 IU/mL) serum HCV-RNA at week 12 and week 24 of treatment, respectively. SVR was confirmed by undetectable serum HCV-RNA at the end of treatment as well as 6 months later. Overall, 43.5% of patients exhibited SVR, 42.6% were nonresponders and 13.9% were relapsers. EVR was observed in 40.74% and LVR in 59.25% of them. The positive predictive values of EVR and LVR were 72.97% and 86.27% whereas their negative predictive values were 64.29% and 92.85%, respectively. EVR independently predicted SVR in Caucasian patients ( P  < 0.001) but not in Egyptian patients ( P  = 0.613), in whom the only independent predictor of SVR was the absence of cirrhosis ( P  = 0.004). LVR seems to be a better predictor of SVR than EVR in the vast majority of genotype 4-infected CHC patients, irrespective of ethnicity and all the other baseline parameters.     

Pegylated Interferon and Ribavirin in the Retreatment of Chronic Hepatitis C in Korea

Background/Aims

Pegylated interferon (peginterferon) and ribavirin is the current standard therapy for chronic hepatitis C. The aims of this study were to evaluate the efficacy of peginterferon and ribavirin and to identify predictors of a sustained virological response (SVR) to the retreatment of chronic hepatitis C in Korea.

Methods

The clinical records of 91 patients with chronic hepatitis C who were retreated with peginterferon and ribavirin were retrospectively analyzed. None of the patients had previously attained a SVR, and the patients were categorized according to their previous responses (nonresponder, relapser, or inadequate treatment) to conventional interferon/ribavirin.

Results

The overall SVR rate was 54.9%. Independent predictors of a SVR were genotypes 2 and 3, relapse, an adherence to peginterferon of over 80%, and an early virological response (EVR). For genotype 1 patients, an adherence to peginterferon of over 80% was an independent predictor of a SVR.

Conclusions

Peginterferon and ribavirin therapy is effective for the retreatment of Korean chronic hepatitis C patients who have failed interferon/ribavirin, especially in patients with genotypes 2 and 3, relapse, an adherence to peginterferon over 80%, and an EVR. For genotype 1 patients, retreatment was effective in patients with an adherence to peginterferon over 80%.     

Early HCV dynamics on Peg-interferon and ribavirin in HIV/HCV co-infection: indications for the investigation of new treatment approaches

OBJECTIVES: To describe the 28-day hepatitis C virus (HCV) kinetics under Pegylated-interferon (Peg-IFN) + ribavirin (RBV) therapy in HIV/HCV co-infected patients. To evaluate the predictive value of early virological response (EVR) of achieving a sustained virological response (SVR). To investigate the baseline mutations in the interferon sensitivity determining region (ISDR)2209-2248 in the non-structural 5A protein of HCV according to genotype. METHODS: Open, prospective trial including 28 co-infected patients with directly observed treatment with Peg-IFN + RBV. We assessed the predictive values of EVR (> or = 2 log10 of HCV decay or a negative qualitative test) at days 1, 7, 28 and in week 12 of the SVR. RESULTS: The SVR in an intention-to-treat analysis was 28.6% (genotype 1, 1/13; genotype 3, 6/10; genotype 4, 1/5). Patients who reached SVR presented a significantly faster HCV plasma viral load reduction compared to non-responders from the first 24 h [-1.06 log10 (interquartile range, -1.7 to -0.4) versus -0.05 log10 (interquartile range, -0.4 to +0.14) respectively; P = 0.002]. The median HCV viral load at week 12 was significantly different from that at baseline in responder and transient responders but not in non-responder patients. The positive predictive value was 100% within the first month and the best negative predictive value was 92% and 88.8% at weeks 4 and 12 respectively. The only genotype 1 responder patient had eight mutations in ISDR2209-2248. CONCLUSIONS: A very early HCV viral decay is observed in responder patients. An early virological response assessment at week 4 and 12 might be a useful tool in the clinical management of the co-infected population.     

Predictive factors of early and sustained responses to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b: amino acid substitutions in the core region and low-density lipoprotein cholesterol levels

BACKGROUND/AIMS: We showed previously that amino acid (aa) substitutions in the HCV core region (HCV-CR) are predictors of non-virological response (NVR) to peginterferon (PEG-IFN) plus ribavirin (RBV) therapy. Here, we determined the predictive factors of sustained virological response (SVR) and early virologic response (EVR) to this treatment. METHODS: We evaluated the response to 48-week PEG-IFN-RBV therapy in 114 Japanese adults infected with HCV genotype 1b and determined the predictors of EVR and SVR. RESULTS: EVR was achieved by 70% and SVR by 45% of patients. 64% of patients who achieved EVR also showed SVR, while none of non-EVR achieved SVR. Multivariate analysis identified low-density lipoprotein cholesterol (LDL-C) (>or=86 mg/dl), aa substitutions in HCV-CR (double-wild-type; arginine at aa 70/leucine at aa 91), gamma-glutamyl transpeptidase (GGT) (<109 IU/l), RBV dose (>or=11.0mg/kg), and leukocyte count (>or=4500/mm3) as significant determinants of EVR, and aa substitutions in HCV-CR (double-wild-type), LDL-C (>or=86 mg/dl), male gender, ICG R15 (<10%), GGT (<109 IU/l), and RBV dose (>or=11.0 mg/kg) as determinants of SVR. Prediction of response to therapy based on combination of these factors had high sensitivity, specificity, positive, and negative predictive values. CONCLUSIONS: Our study identified aa substitutions in the core region and serum LDL-C as predictors of response to PEG-IFN-RBV therapy in Japanese patients infected with HCV genotype 1b.     

High predictive value of early viral kinetics in retreatment with peginterferon and ribavirin of chronic hepatitis C patients non-responders to standard combination therapy

BACKGROUND/AIMS: To evaluate the efficacy of peginterferon alfa-2b and ribavirin in unselected consecutive patients with chronic hepatitis C, treated outside of trials, who were relapsers or non-responders to interferon and ribavirin combination. METHODS: One hundred and fifty-four patients were evaluated. There were 101 non-responders and 53 relapsers to standard combination therapy. Patients were retreated with peginterferon alfa-2b 1.5 microg/kg/wk plus ribavirin 1000-1200 mg/day during 48 weeks. RESULTS: Forty-four patients (28.6%) achieved sustained virological response (SVR). Rapid (week 4) and early (week 12) virological response had high negative predictive values of SVR (94% and 97%, respectively); however positive predictive values were relatively low (52% and 49%, respectively). Relapsers had higher SVR rates (58.5%) than non-responders (13%) p<0.0001. In non-responders, SVR raised to 50% in patients with genotype non-1 and mild or moderate fibrosis. In multivariate analysis, predictors of SVR were: relapse after interferon plus ribavirin combination, mild or moderate fibrosis, genotype non-1 and baseline viral load <2 million copies/ml. CONCLUSIONS: Relapsers to interferon plus ribavirin therapy, and non-responders with genotype non-1 and mild or moderate fibrosis, achieved a relatively high SVR rate following retreatment with peginterferon plus ribavirin. Early viral kinetics had a high negative predictive value of SVR.